Objectives To determine if the restriction of dietary caloric intake (but without malnutrition) can retard the rate of aging in a primate species. ABSTRACT:Minimum of 150 words and maximum of 300 words. Dietary restriction (DR) is a major paradigm in gerontology because only DR retards the rate of aging in rodents. Whether DR retards aging in primates is unknown. We hypothesize that DR influences aging processes in a primate species like it does in rodents and that this influence is reflected by an altered rate of change of certain physiologic parameters of aging. There are two Specific Aims 1) to contribute to the development of the rhesus monkey as a model for the study of aging, and 2) to determine the influence of DR on the rate of aging in a primate species. We seek to improve understanding of aging in this species and to develop more precise ways to monitor the aging rate. We are studying longitudinally three Cohorts of DR and Control rhesus monkeys. Cohort 1 n=14/group, males (studied since 1989). We are adding Cohort 2 n=15/group, 8-14 yr old females to be followed as per Cohort 1, and Cohort 3 n=8/group, 8-14 yr old males also undergoing biopsy of liver, spleen and skeletal muscle to allow comparison of DR's influences in tissues well studied in rodents on DR. There are three projects linked by a common theme of energy metabolism because the magnitude of DR's effects in rodents is related strongly to energy intake. We hypothesize that adjustments of energy and free radical metabolism are major mechanisms in DR's ability to retard aging. Project 1 ("The Mitochondrion DNA Integrity and Enzyme Activities") assesses the influence of DR and aging on mitochondrial function and DNA integrity (deletions, oxidized bases). Project 2 ("Energy Balance and Insulin Sensitivity") examines the impact of aging and DR on energy metabolism and glucose utilization. Project 3 ("Biomarkers of Aging") quantitates the rate of aging in these Cohorts. Keywords caloric intake, mitochondria, mitochondrial DNA abnormalities, biomarkers of aging, cytokines, glucoregulation